This Article Full Text Full Text (PDF) Supplemental material Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Obert, C. Articles by Orihuela, C. J. Search for Related Content PubMed PubMed Citation Articles by Obert, C. Articles by Orihuela, C. J.

 Previous Article  |  Next Article 

Infection and Immunity, August 2006, p. 4766-4777, Vol. 74, No. 8
0019-9567/06/$08.00+0     doi:10.1128/IAI.00316-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Identification of a Candidate Streptococcus pneumoniae Core Genome and Regions of Diversity Correlated with Invasive Pneumococcal Disease

Caroline Obert,^1, Jack Sublett,^1, Deepak Kaushal,² Ernesto Hinojosa,³ Theresa Barton,⁴ Elaine I. Tuomanen,¹ and Carlos J. Orihuela^1*

Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee 38105,¹ Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee 38105,² Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229,³ Department of Pediatrics, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390⁴

Received 24 February 2006/ Returned for modification 13 April 2006/ Accepted 10 May 2006

Streptococcus pneumoniae is a leading cause of community-acquired pneumonia and gram-positive sepsis. While multiple virulence determinants have been identified, the combination of features that determines the propensity of an isolate to cause invasive pneumococcal disease (IPD) remains unknown. In this study, we determined the genetic composition of 42 invasive and 30 noninvasive clinical isolates of serotypes 6A, 6B, and 14 by comparative genomic hybridization. Comparison of the present/absent gene matrix (i.e., comparative genomic analysis [CGA]) identified a candidate core genome consisting of 1,553 genes (73% of the TIGR4 genome), 154 genes whose presence correlated with the ability to cause IPD, and 176 genes whose presence correlated with the noninvasive phenotype. Genes identified by CGA were cross-referenced with the published signature-tagged mutagenesis studies, which served to identify core and IPD-correlated genes required for in vivo passage. Among these, two pathogenicity islands, region of diversity 8a (RD8a), which encodes a neuraminidase and V-type sodium synthase, and RD10, which encodes PsrP, a protein homologous to the platelet adhesin GspB in Streptococcus gordonii, were identified. Mice infected with a PsrP mutant were delayed in the development of bacteremia and demonstrated reduced mortality versus wild-type-infected controls. Finally, the presence of seven RDs was determined to correlate with the noninvasive phenotype, a finding that suggests some RDs may contribute to asymptomatic colonization. In conclusion, RDs are unequally distributed between invasive and noninvasive isolates, RD8a and RD10 are correlated with the propensity of an isolate to cause IPD, and PsrP is required for full virulence in mice.

Supplemental material for this article may be found at http://iai.asm.org/.

Editor: J. N. Weiser

C.O. and J.S. contributed equally to the manuscript.

This article has been cited by other articles:

• Rosch, J. W., Mann, B., Thornton, J., Sublett, J., Tuomanen, E. (2008). Convergence of Regulatory Networks on the Pilus Locus of Streptococcus pneumoniae. Infect. Immun. 76: 3187-3196 [Abstract] [Full Text]  
• Bu, S., Li, Y., Zhou, M., Azadin, P., Zeng, M., Fives-Taylor, P., Wu, H. (2008). Interaction between Two Putative Glycosyltransferases Is Required for Glycosylation of a Serine-Rich Streptococcal Adhesin. J. Bacteriol. 190: 1256-1266 [Abstract] [Full Text]  
• Burnaugh, A. M., Frantz, L. J., King, S. J. (2008). Growth of Streptococcus pneumoniae on Human Glycoconjugates Is Dependent upon the Sequential Activity of Bacterial Exoglycosidases. J. Bacteriol. 190: 221-230 [Abstract] [Full Text]  
• Bensing, B. A., Siboo, I. R., Sullam, P. M. (2007). Glycine Residues in the Hydrophobic Core of the GspB Signal Sequence Route Export toward the Accessory Sec Pathway. J. Bacteriol. 189: 3846-3854 [Abstract] [Full Text]  
• Bijlsma, J. J. E., Burghout, P., Kloosterman, T. G., Bootsma, H. J., de Jong, A., Hermans, P. W. M., Kuipers, O. P. (2007). Development of Genomic Array Footprinting for Identification of Conditionally Essential Genes in Streptococcus pneumoniae. Appl. Environ. Microbiol. 73: 1514-1524 [Abstract] [Full Text]  
• Obert, C. A., Miller, M. L., Montgomery, J., Adamkiewicz, T., Tuomanen, E. I. (2007). Quinupristin-Dalfopristin Nonsusceptibility in Pneumococci from Sickle Cell Disease Patients. Antimicrob. Agents Chemother. 51: 386-389 [Abstract] [Full Text]